The candidate tumour suppressor p33ING1cooperates with p53 in cell growth control

Abstract

The candidate tumour-suppressor gene ING1 has been identified by using the genetic suppressor element (GSE) methodology¹. ING1 encodes a nuclear protein, p33^ING1, overexpression of which inhibits growth of different cell lines. The properties of p33^ING1suggest its involvement in the negative regulation of cell proliferation and in the control of cellular ageing, anchorage dependence and apoptosis^1,2,3. These cellular functions depend largely on the activity of p53, a tumour-suppressor gene that determines the cellular response to various types of stress⁴. Here we report that the biological effects of ING1 and p53 are interrelated and require the activity of both genes: neither of the two genes can, on its own, cause growth inhibition when the other one is suppressed. Furthermore, activation of transcription from the p21/WAF1 promoter, a key mechanism of p53-mediated growth control, depends on the expression of ING1. A physical association between p33^ING1and p53 proteins has been detected by immunoprecipitation. These results indicate that p33^ING1is a component of the p53 signalling pathway that cooperates with p53 in the negative regulation of cell proliferation by modulating p53-dependent transcriptional activation.